Qualitative SAR

This is the realm of in silica simulations, text mining, database management, classic in silica qualitative SAR modeling and physiology modeling. 

SAR is a relationship of a particular chemical s structure with its physical/ chemical properties and its human health effect. Conceptually, these relationships are either qualitative or quantitative in nature. Qualitative SAR... 

Potential concerns for a constituent of an additive raised by a qualitative SAR analysis may be addressable by a more in-depth, quantitative SAR (QS AR) analysis. The approach to QSAR used in the food contact notification program is to identify the most appropriate specific structural analogs from the pool of chemicals for which adequate carcinogenicity data are available. If, in the expert judgment of FDA reviewers, the analogs can reasonably be considered to be as toxic or more toxic than the compound of concern, these analogs can be used to develop a quantitative estimate of its upper bound LCR. 

Table 4.2 Summary of crystallographic data used for qualitative SAR analysis.

Shown are PDB accession codes and similarity and potency data for complex crystal structures subjected to qualitative SAR analysis. The table is adapted from the supplementary material of. ... 

Discontinuous SARs. Consistent with the results of our qualitative SAR analysis presented above, SARI scoring indicates that ribonuclease A inhibitors are a prototypic example of discontinuous SARs. The potency among these highly similar nucleotide analogs differs by up to three orders of magnitude (Figure 4.7b). As already mentioned above, these features clearly indicate the presence of discontinuous SARs. The low SARI score of 0.16 mirrors these findings. It results from the combination of a very low continuity score of nearly zero (0.004) that reflects the lack of structural diversity within the... 

In practice, often the combination of qualitative SAR analysis with local or global models capturing SAR trends on a more quantitative basis are effective in the design phase for novel derivatives. If these models are based on local chemical environments coupled with interpietable chemical descriptors and preferentially a linear statistical approach for data modeling, those could potentially have a high impact on decisions taken during lead optimization and progressing a project effectively toward the next milestone. 

Nifedipine was used as lead compound in order to carry out qualitative SAR studies for DHPs to determine the most significant structural components that affect the activity of DHPs. Such studies reveal ... 

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